It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies.

Cognitive impairments are central to schizophrenia, but their clinical utility for tagging heterogeneity in lifetime outcome and response to treatment is not conclusive. By exploiting four cognitive domains consistently showing large deficits in studies, we tested whether cluster analysis would define separate subsets of patients and then whether the disease heterogeneity marked by these clusters would be related to lifetime outcome and response to treatment. A total of 112 schizophrenia patients completed a neuropsychological evaluation. The PANSS, GAF-S and GAF-F were rated at the onset and endpoint of the illness trajectory. A blind judgment of the lifetime response to treatment was made. The first cluster presented near-normal cognitive performance. Two other clusters of severely impaired patients were identified: one generally impaired in the four cognitive domains and another selectively impaired in visual episodic memory and processing speed, each relating to a different lifetime evolution of disease and treatment response. Although the two impaired clusters were clinically indistinguishable in symptom severity and functioning at disease onset, patients with selective cognitive impairments demonstrated better improvement at outcome, whereas the generally impaired patients were more likely to be treatment refractory. The findings have implications for the management of patients and for clinical trials since particular combinations of cognitive deficits in patients would influence their treatment response.

OBJECTIVE: Meta-analysis results confirm that cognitive-behavioural therapy in psychosis (CBTp) is efficient for persistent symptoms. However, external validity remains unexplored. CBTp in early psychosis (in the first 5 years after diagnosis) seems especially relevant, given a possible impact on long-term course. However, the few studies that experimented with CBTp with this population had poor results. They all introduced therapy during an acute psychotic phase and most of them performed a limited number of sessions. Therefore, our introductory open study aimed to evaluate the efficiency of a 25-session Australian CBTp program, introduced during a stable phase in Quebec patients with early psychosis.

METHOD: The Active Cognitive Psychotherapy for Early Psychosis program was offered to 20 patients aged 14 years or older, at a rate of 1 weekly session during 6 months.

RESULTS: The acceptance rate was 75%, the mean session compliance rate was 84%, and participants were satisfied with the program. Pre- and post-CBTp analyses indicated statistically significant improvements of psychotic symptomatology, which were maintained at 6-month follow-up. Self-criticism improvement was also statistically significant, post-CBTp.

CONCLUSION: CBTp seems to be appropriate in our clinical settings, including with adolescents. Moreover, the treatment dosage used seems to foster session compliance.

The objective of this article is to decompose the level of functioning phenotype in autism to see if it can be conceptualized as two simpler, but still familial, dimensional phenotypes of language and non-verbal IQ. We assembled 80 sibpairs with either autism, Asperger syndrome or atypical autism. To see whether the familial correlation on language scores was accounted for by the familial correlation on non-verbal IQ, residual language scores were calculated for each member of the sibpair based on a multiple regression equation using their IQ score as an explanatory or independent variable and controlling for the age and gender of the affected individual. These residual scores were then used to calculate intraclass correlations between affected sibs. This process was repeated using IQ as the dependent variable and language as a covariate. Within affected individuals there was a strong relation between non-verbal IQ (as measured by the Leiter performance scale) and language (as measured by the Vineland Communication Scale). In addition, there was familial correlation between sibs on both measures. Evidence of familial aggregation on both non-verbal IQ and language remained even after partialling out the effect of the covariates by regression analysis and by generalized estimating equation. These findings suggest that non-verbal IQ and language in PDD may arise from independent genetic mechanisms. The implications of this finding for linkage analysis and for identifying genetically informative phenotypes are discussed.

In a previous study [Maziade et al. (2005); Mol Psychiatry 10:486-499], we provided evidence for linkage (parametric lod score of 4.05) on chromosome 16p for bipolar affective disorder (BP) in 21 kindreds from Eastern Quebec, a population characterized by a founder effect. Using a stringent design, we performed a replication study in a second sample of 27 kindreds (sample 2) collected from the same population and assessed with the same methodologies as in our original sample (sample 1), that is with the same diagnostic procedure and using a common set of 23 markers studied with model-based (parametric) and model-free (nonparametric) linkage analyses. We replicated our initial finding with P values <0.001. Indeed, maximum NPL(all) scores of 3.7 and 3.52 were found at marker D16S3060 in sample 2 for the narrow and broad BP phenotype definition, respectively. For the latter definition, the nonparametric score reached 3.87 in the combined sample, a value that exceeded the maximum NPL score obtained in each individual sample (NPL(all) = 2.32 in sample 1; NPL(all) = 3.52 in sample 2). Moreover, a refined phenotype restricted to BP associated with psychosis yielded significant evidence for linkage in each individual sample (NPL(all) = 2.38 in sample 1; NPL(all) = 2.72) while yielding the best result (NPL(all) score = 3.90) in the combined sample (samples 1 and 2), despite an important reduction in the number of affected individuals. It is also noteworthy that the use of the refined phenotype provided a location of the maximum linkage peak shared by both samples, that is, at marker D16S668 in 16p13.12, suggesting consistency across samples. Our study provided one of the strongest pieces of evidence for linkage with BP in 16p and illustrated the heuristic potential of a replication study in a second sample ascertained from the same population and using homogeneous methodologies.

This article seeks to validate the French translation of the Strauss and Carpenter revised outcome criteria scale (SCOCS-R) through the study of its interrater reliability, its convergent validity, and its factor structure. Using a sample of 113 DSM-IV schizophrenic subjects, we assessed the interrater reliability of the SCOCS-R and its convergent validity with an already validated scale (Social and Occupational Functioning Assessment Scale). The factor structure of the SCOCS-R was assessed using a principal components analysis. Interrater reliability was excellent (ri > or = 0.88 for each of the individual items), and the convergent validity with the Social and Occupational Functioning Assessment Scale proved to be highly satisfactory (r = 0.89; p < .0001). Factor analyses yielded two factors corresponding to social functioning and professional functioning. These factors accounted for 78% of the variance of outcome. These results demonstrate the reliability and the validity of the French translation of the SCOCS-R. Moreover, the two dimensions yielded by our factor analysis add to the evidence of the multidimensional structure of outcome. This article supports the relevance of the SCOCS-R to assess the dimensions of outcome in schizophrenic subjects.

OBJECTIVE: To identify neuropsychological domains, including fine motor dexterity, that are related to social functioning in schizophrenia.

METHOD: Thirty-six DSM-IV schizophrenic subjects were assessed using the Purdue Pegboard test, the Modified Wisconsin Card Sorting test, the Tower of London, Schwartz' Reaction Time and Wechsler's Associate Learning and Digit Span tests. Social functioning was measured by the Social and Occupational Functional Assessment Scale.

RESULTS: Univariate regression analyses showed that the Purdue Pegboard, the Modified Card Sorting test, the Tower of London and Wechsler's Associate Learning subtest were significantly linked to social functioning. The best fitting multivariate model to explain social functioning included fine motor dexterity and executive functioning.

CONCLUSION: Various neuropsychological measures correlated to social functioning, the correlation involving fine motor dexterity being the strongest one. Future studies of the prediction of social functioning in schizophrenia should include fine motor dexterity.

A double-labeling protocol was used to determine how cells with different angular preferences to whisker motion distribute across the dimensions of a barreloid in the ventral posterior medial nucleus of the rat thalamus. Individual barreloids were labeled retrogradely by injecting Fluoro-Gold in identified barrel columns, and single relay cells (n = 30) pertaining to the labeled barreloids were stained juxtacellularly with Neurobiotin after determination of their angular tuning preference to controlled whisker deflection. Results show that cells with like angular preference are clustered within the barreloids. Those best tuned to forward and upward directions are located principally in the dorsal sector of the barreloid, whereas those best tuned to backward and downward motion are located principally in the central and ventral sectors, respectively. The relationship between cell location and angular preference was assessed by regression, cluster, and discriminant analysis. Together, these tests indicate that barreloids contain a map of shifting angular preference that transposes along the length of a barreloid directional property imposed at the periphery by the circumferential distribution of receptors around the vibrissa follicles.

OBJECTIVE: This is the first study to report a direct comparison of neuropsychological performance in Kraepelinian vs. non-Kraepelinian schizophrenia (SZ).

METHODS: 17 Kraepelinian and 19 non-Kraepelinian subjects were assessed on a neuropsychological battery including the Purdue Pegboard, Schwartz' Reaction Time task, the Modified Card Sorting Test, the Wechsler's Associate Learning Test and the Digit Span.

RESULTS: Kraepelinian schizophrenia was characterized by more impaired performance on the Purdue Pegboard and the Card Sorting test. These differences remained significant when introducing, as covariates, the type of neuroleptic used, the use of anticholinergic medication, age and gender. Differences on the Reaction Time, the Associate Learning and the Digit Span tasks did not reach statistical significance.

CONCLUSIONS: These results suggest that Kraepelinian schizophrenia is characterized by impaired performance on fine motor dexterity and executive functioning. These results further add to the evidence for the validity of the distinction between Kraepelinian and non-Kraepelinian schizophrenia as a strategy to better understand the factors influencing severity and/or outcome in schizophrenia.